Are the (New) Synthetic Opioids U-47700, Tramadol and Their Main Metabolites Prone to Time-Dependent Postmortem...

Area of Science:

• Forensic Toxicology
• Pharmacokinetics
• Analytical Chemistry

Background:

• Interpreting forensic postmortem (PM) analytical results is challenging due to postmortem redistribution (PMR).
• Data on new synthetic opioids, including dose and timing, are scarce, complicating PMR analysis.
• Controlled studies are needed to understand PMR for emerging synthetic opioids.

Purpose of the Study:

• To investigate the postmortem tissue distribution and PMR of U-47700 and tramadol.
• To examine the PMR of the main metabolites: N-desmethyl-U-47700 and O-desmethyltramadol (ODT).
• To determine the most suitable biological matrix for quantifying these substances in postmortem cases.

Main Methods:

• A controlled toxicokinetic study using 12 domestic pigs was conducted.
• Pigs received intravenous doses of U-47700 (100 µg/kg BW) or tramadol (1,000 µg/kg BW).
• Samples were collected at 8 hours post-administration and at 24, 48, and 72 hours postmortem (PM) after storage at room temperature (RT). Quantification was performed using LC-MS/MS.

Main Results:

• U-47700, tramadol, and their metabolites showed only low-to-moderate concentration changes in most tissues and fluids during RT storage.
• A significant concentration increase of tramadol was observed specifically in liver tissue.
• These findings suggest limited PMR for U-47700 and tramadol and their metabolites.

Conclusions:

• Synthetic opioids U-47700 and tramadol, along with their primary metabolites, exhibit low susceptibility to postmortem redistribution.
• Central blood is identified as a potentially reliable matrix for the quantification of these substances in forensic investigations.
• The study provides crucial toxicokinetic data for interpreting analytical results in postmortem cases involving these synthetic opioids.